Conventional direct emulsions consist of an oily phase dispersed in the form of droplets in a continuous aqueous phase. Direct fluorocarbon emulsions wherein the fluorocarbon is the oily phase have been used in various biomedical applications. Because of the high oxygen-carrying capacity of fluorocarbons, such fluorocarbon emulsions are particularly useful as blood substitutes to provide oxygen to the vascular system. After introduction of the emulsions, the oxygen dissolved in the dispersed fluorocarbon phase is released into the blood. Other medical uses include the treatment of cardiovascular and cerebrovascular diseases, coronary angioplasty, organ preservation and cancer therapy; diagnostic uses such as nuclear magnetic resonance and ultrasound; and veterinary therapy (Riess J. G., Blood Compatible Materials and Devices": Perspective Towards the 21st Century, Technomics Publishing Co., Lancaster, Pa., Ch. 14, 1991; Riess, J. G., Vox. Sang., 61:225, 1991). Conventional direct fluorocarbon emulsions have been described in, for example, EP-A-0 255 443, FR-A- 2 665 705, FR-A- 2 677 360, FR-A- 2 694 559, FR-A- 2 679 150, WO-A-93 01798, WO90/15807, EP-A-311473 and US 3,975,512.
The pulmonary administration of drugs constitutes a difficult problem because the introduction of drugs directly into the lungs cannot be effectively achieved by means of an aqueous solution. Fluorocarbon direct emulsions wherein the continuous phase is water are unsuitable for pulmonary drug delivery for the same reason.
The use of fluorocarbon liquids for pulmonary ventilation and drug administration via the pulmonary route has been described by Shaffer et al. (Art. Blood Subs. and Cells Immob. Biotech., 22:1994Pediatr. Pulmonol., 14:102, 1992) who contemplated the use of pure fluorocarbon liquids containing a dispersion of drugs in the form of solid powders. These compositions, however, result in non-homogenous, unreliable and irreproducible drug delivery due to the dispersion of the powdered agent in the fluorocarbon phase.
PCT Application No. WO91/18613 describes autoemulsifying "glasses" useful for the generation of reverse or multiple emulsions by contacting the "glass" with an appropriate aqueous phase. This document describes neither fluorinated nor non-fluorinated surfactants. Stable reverse fluorocarbon emulsions capable of effective intrapulmonary drug delivery are not disclosed.
EP-A-0-250 766 describes perfluoropolyether microemulsions of the water-in-oil type to be used as lubricants; these microemulsions contain low amounts of fluorocarbon (ca. 13-30% v/v).
Japanese Patent 57/109714 describes delivery of an anticancer agent to a desired site by mixing the agent with a magnetic fluid and applying a magnetic field to the resulting mixture. These fluids may be in the form of direct emulsions, reverse emulsions or multiple emulsions for intravascular administration. Again, this document does not describe stable reverse emulsions suitable for intrapulmonary drug delivery.
Thus, there is a need for stable fluorocarbon emulsions capable of homogeneous, reproducible pulmonary drug delivery in a controlled manner. The present invention satisfies this need.
The same preparations with a fluorocarbon as the continuous phase can be further utilized to deliver drugs and other materials to other body cavities including the gastrointestinal tract, peritoneal cavity, pleural cavity, subarachnoid ventricular spaces, etc.